1. Field of the Invention
The present invention relates to a measurement of a concentration of a component in a subject. More particularly, the present invention relates to a method and apparatus for accurately measuring a concentration of a component in a subject, such as a bodily fluid in a human body, by removing a time difference between a measurement of a reference light and a measurement of a signal light.
2. Description of the Related Art
With overall improvements in quality of life and living conditions, interest in personal health has increased. As a result, a wide array of home medical equipment that allows people to easily monitor their personal health has been researched and developed. In a normal human body, bodily fluid is organically circulated and adjusted so that an amount of bodily fluid is maintained within a predetermined range. Bodily fluids include blood, urine, interstitial fluid, sweat, and saliva. In particular, concentrations of blood and urine (glucose and protein) are essential parameters in determining a person's state of health. In addition, concentrations of blood components, such as glucose, hemoglobin, bilirubin, cholesterol, albumin, creatinine, protein, and urea, play an important role in assessing a person's state of health.
When a human body is infected with a disease, a composition or a volume of a component in a bodily fluid changes, which may result in death. For example, a normal person's blood glucose concentration is about 80 mg/dl before a meal and about 120 mg/dl after a meal. In order to maintain such a normal glucose concentration, a human pancreas secretes an appropriate amount of insulin before or after the meal so that glucose can be absorbed into the liver and skeletal muscle cells. However, when the pancreas does not secrete an appropriate amount of insulin to maintain a normal blood glucose concentration due to a disease or other causes, an excessive amount of glucose exists in the blood, which causes diseases of the heart or liver, arteriosclerosis, hypertension, cataract, retinal bleeding, nerve damage, hearing loss, or visual impairment, all of which may cause serious problems including death. Accordingly, a technique of measuring a change in a bodily fluid in a human body is considered very important.
Methods of measuring the concentration of a component of bodily fluid include invasive methods of directly collecting a sample from a subject and gathering measurements on the collected part of the subject and noninvasive methods of gathering measurements without directly collecting a sample from a subject. Since invasive methods have many problems, techniques of easily analyzing components of bodily fluid using a noninvasive method have been continuously researched and developed. Conventionally, when measuring a component of bodily fluid, for example, blood glucose, blood is extracted, reacted with a reagent, and then analyzed by using a clinical analysis system or quantifying a change in the color of a test strip. When such a blood glucose test is performed daily, a patient suffers from pain resulting from the direct blood collection and is susceptible to infection. Moreover, since it is difficult to continuously monitor the blood glucose level, it is difficult to properly treat a patient in an emergency situation. In addition, use of disposable strips and reagents may be a financial burden on the patient. Furthermore, these disposable strips and reagents cause environmental contamination, and as such, require special treatment. Accordingly, development of a technique of measuring a blood glucose concentration without extracting blood is desired for monitoring and adjusting the blood glucose level of a diabetic or diagnosing a person's state of health. Many methods of noninvasively measuring blood glucose have been researched, but instruments using these methods have not been commercialized.
In most conventional, spectroscopic methods of measuring the concentration of a blood component in a human body, light within a visible ray and near infrared ray (NIR) wavelength range is radiated onto a part of the human body, and then, light reflected from or transmitted through the human body is detected. In such spectroscopic methods, a spectrum is usually measured to measure the concentration of a blood component. Here, a reference light source having a wavelength that responds best to a blood component to be measured and a bandwidth that effectively counterbalances an influence of an interference substance is required. Conventionally, a continuous wave (CW) lamp is used as a light source, and the intensity of the light is measured using an expensive array detector, or a spectrum is measured using a spectroscopic system, in order to calculate the concentration of a component. Alternatively, a light emitting diode (LED) or a laser diode (LD) may be used as the light source.
However, since the concentration of a component to be measured may be very low in blood and a light diffusion effect is greater than a light absorption effect in living tissue and blood, detected signals are very weak. Thus, a method of amplifying the signal is required. Moreover, since organic substances in a human body continuously flow, a component concentration can be accurately measured only when the measurement is quickly performed. In addition, it must be noted that an average energy radiated onto a human body should not go beyond a limit that may damage the human body. In particular, in an NIR wavelength range of 700 through 2500 nm, a glucose absorption band is widely distributed, but a maximum absorption of glucose is small as compared to a large aqueous background spectrum. Resultantly, a signal to noise ratio (SNR) is small, which makes accurate measurements very difficult.
In various conventional, non-invasive methods of measuring a concentration of a component in a subject, absorbance is measured, and a multivariate statistical analysis is performed on the absorbance to analyze a component concentration. The absorbance can be expressed as a negative log ratio between signal light intensity measured from a sample and reference light intensity. Since the reference light intensity measured without a human body and the signal light intensity measured from the human body are measured at predetermined time intervals, a time difference exists between the measurement of the signal light intensity and the measurement of the reference light intensity. Such a time difference can be removed by simultaneously measuring the reference light intensity and the signal light intensity. In a conventional approach for removing the time difference, a beam is split into two beams by a beam splitter before being radiated onto a human body. One of the two beams is sent to a reference light intensity channel, and the other is sent to a signal light intensity channel. Intensities of these two beams are separately measured and used to predict the concentration of a particular component. In this situation, however, an additional optical system for splitting an input beam and related parts are required. Therefore, it is difficult to construct a compact system. Meanwhile, when a beam splitter is not used, the reference light intensity is measured first, then the signal light intensity is measured in order to calculate absorbance. However, due to influences of various changes occurring during an interval of time between the measurement of the reference light intensity and the measurement of the signal light intensity, it is difficult to accurately predict the concentration of a component.